PMID- 18292209
OWN - NLM
STAT- MEDLINE
DCOM- 20080728
LR  - 20211020
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 26
IP  - 5
DP  - 2008 May
TI  - Immunogenicity of human mesenchymal stem cells in HLA-class I-restricted T-cell 
      responses against viral or tumor-associated antigens.
PG  - 1275-87
LID - 10.1634/stemcells.2007-0878 [doi]
AB  - Human mesenchymal stem cells (MSC) are immunosuppressive and poorly immunogenic 
      but may act as antigen-presenting cells (APC) for CD4(+) T-cell responses; here 
      we have investigated their ability to serve as APC for in vitro CD8(+) T-cell 
      responses. MSC pulsed with peptides from viral antigens evoked interferon 
      (IFN)-gamma and Granzyme B secretion in specific cytotoxic T lymphocytes (CTL) 
      and were lysed, although with low efficiency. MSC transfected with tumor mRNA or 
      infected with a viral vector carrying the Hepatitis C virus NS3Ag gene induced 
      cytokine release but were not killed by specific CTL, even following pretreatment 
      with IFN-gamma. To investigate the mechanisms involved in MSC resistance to 
      CTL-mediated lysis, we analyzed expression of human leukocyte antigen (HLA) class 
      I-related antigen-processing machinery (APM) components and of immunosuppressive 
      HLA-G molecules in MSC. The LMP7, LMP10, and ERp57 components were not expressed 
      and the MB-1 and zeta molecules were downregulated in MSC either unmanipulated or 
      pretreated with IFN-gamma. Surface HLA-G was constitutively expressed on MSC but 
      was not involved in their protection from CTL-mediated lysis. MSC supernatants 
      containing soluble HLA-G (sHLA-G) inhibited CTL-mediated lysis, whereas those 
      lacking sHLA-G did not. The role of sHLA-G in such inhibition was unambiguously 
      demonstrated by partial restoration of lysis following sHLA-G depletion from MSC 
      supernatants. In conclusion, human MSC can process and present HLA class 
      I-restricted viral or tumor antigens to specific CTL with a limited efficiency, 
      likely because of some defects in APM components. However, they are protected 
      from CTL-mediated lysis through a mechanism that is partly sHLA-G-dependent.
FAU - Morandi, Fabio
AU  - Morandi F
AD  - Laboratory of Oncology, G. Gaslini Children's Hospital, Genoa, Italy. 
      fabiomorandi@ospedale-gaslini.ge.it
FAU - Raffaghello, Lizzia
AU  - Raffaghello L
FAU - Bianchi, Giovanna
AU  - Bianchi G
FAU - Meloni, Francesca
AU  - Meloni F
FAU - Salis, Annalisa
AU  - Salis A
FAU - Millo, Enrico
AU  - Millo E
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Barnaba, Vincenzo
AU  - Barnaba V
FAU - Pistoia, Vito
AU  - Pistoia V
LA  - eng
GR  - R01 CA138188/CA/NCI NIH HHS/United States
GR  - R01-CA110249/CA/NCI NIH HHS/United States
GR  - P01 CA109688/CA/NCI NIH HHS/United States
GR  - R01 CA110249-03/CA/NCI NIH HHS/United States
GR  - P01-CA109688/CA/NCI NIH HHS/United States
GR  - R01 CA105500/CA/NCI NIH HHS/United States
GR  - R01 CA067108/CA/NCI NIH HHS/United States
GR  - R01 CA138188-01/CA/NCI NIH HHS/United States
GR  - R01 CA110249/CA/NCI NIH HHS/United States
GR  - R01-CA67108/CA/NCI NIH HHS/United States
GR  - R01 CA105500-05/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080221
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Viral)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - 0 (SERPINB9 protein, human)
RN  - 0 (Serpins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Antigen Presentation/drug effects/immunology
MH  - Antigen-Presenting Cells/cytology/drug effects/immunology
MH  - Antigens, Neoplasm/*immunology
MH  - Antigens, Viral/*immunology
MH  - Cell Line
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Granzymes/antagonists & inhibitors
MH  - HLA Antigens/immunology
MH  - HLA-G Antigens
MH  - Hepacivirus/drug effects/immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immune Tolerance/drug effects
MH  - Immunophenotyping
MH  - Interferon-gamma/pharmacology
MH  - Mesenchymal Stem Cells/drug effects/enzymology/*immunology
MH  - Peptides/immunology
MH  - Serpins/metabolism
MH  - Solubility/drug effects
MH  - T-Lymphocytes/drug effects/*immunology
MH  - T-Lymphocytes, Cytotoxic
PMC - PMC2726787
MID - NIHMS129777
EDAT- 2008/02/23 09:00
MHDA- 2008/07/29 09:00
PMCR- 2009/08/13
CRDT- 2008/02/23 09:00
PHST- 2008/02/23 09:00 [pubmed]
PHST- 2008/07/29 09:00 [medline]
PHST- 2008/02/23 09:00 [entrez]
PHST- 2009/08/13 00:00 [pmc-release]
AID - 2007-0878 [pii]
AID - 10.1634/stemcells.2007-0878 [doi]
PST - ppublish
SO  - Stem Cells. 2008 May;26(5):1275-87. doi: 10.1634/stemcells.2007-0878. Epub 2008 
      Feb 21.